Main Article Content

Donald R Mattison


Sex differences, pharmacokinetics, pharmacodynamics, bioequivalence, drug disposition, adverse drug reactions, adverse drug events


Practitioners are often troubled by the lack of well characterized data on appropriate drug dosing, on effectiveness of treatment, and on drug safety for women and for women in pregnancy. We continue to struggle with how to best treat women during pregnancy and with the real life sex and gender differences in drug pharmacokinetics. This presentation looks at sex differences as a platform for considering the pharmacological status of women and how pregnancy changes that status. Specific examples of sex and gender differences in drug disposition/pharmacokinetics are discussed. The examples describe how sex-based differences influence treatment options and goals.

Abstract 283 | PDF Downloads 293


1. Schwartz JB. Drug metabolism. In: Legato MJ, Bilezikian JP (eds). Principles of Gender-Specific Medicine. Amsterdam; Boston: Elsevier Academic Press, 2004.
2. U.S. Food and Drug Administration. Zolpidem Containing Products: Drug Safety Communication - FDA Requires Lower Recommended Doses. (January 10, 2013) (May 15, 2013).
3. ICRP, 2002. Basic Anatomical and Physiological Data for Use in Radiological Protection Reference Values. ICRP Publication 89. Ann ICRP. 32:3-4.
4. (May 21, 2013)
5. Barquín J, Luna Jde D, Hernández AF. A controlled study of the time-course of breath alcohol concentration after moderate ingestion of ethanol following a social drinking session. Forensic Sci Int 2008;177(2-3):140-145.
6. Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. Arch Intern Med 2007;167(16):1752-1759.
7. Tran C, Knowles SR, Liu BA, Shear NH. Gender differences in adverse drug reactions. J Clin Pharmacol 1998;38(11):1003-1009.
8. Zopf Y, Rabe C, Neubert A, Hahn EG, Dormann H. Risk factors associated with adverse drug reactions following hospital admission: a prospective analysis of 907 patients in two German university hospitals. Drug Saf 2008;31(9):789-798.
9. Evans RS, Lloyd JF, Stoddard GJ, Nebeker JR, Samore MH. Risk factors for adverse drug events: a 10-year analysis. Ann Pharmacother 2005;39(7-8):1161-1168.
10. Mattison Faye ACM, Mattison DR. Drug disposition and effect. In: Schenck-Gustafsson K, DeCola PR, Pfaff DW, Pisetsky DS, eds. Handbook of Clinical Gender Medicine. Basel: Karger, 2012:473-479.
11. United States General Accounting Office. Drug safety: most drugs withdrawn in recent years had greater health risks for women. GAO-01-286R Drugs Withdrawn From Market. January 19, 2001. (June 15, 2013)
12. Davies EC, Green CF, Mottram DR, Pirmohamed M. Adverse drug reactions in hospitals: a narrative review. Curr Drug Saf 2007;2(1):79-87.
13. Anthony M, Berg MJ. Biologic and molecular mechanisms for sex differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics: Part I. J Womens Health Gend Based Med 2002;11(7):601-615.
14. Anthony M, Berg MJ. Biologic and molecular mechanisms for sex differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics: Part II. J Womens Health Gend Based Med 2002;11(7):617-629.
15. Legato MJ. Gender-specific medicine: the view from Salzburg. Gend Med 2004;1(2):61-63.
16. Legato MJ. The skewed sex distribution in affective disorders--a diagnostic, social, or biological problem? Prog Brain Res 2010;186:159-166.
17. Poon S, Goodman SG, Yan RT, Bugiardini R, Bierman AS, Eagle KA, Johnston N, Huynh T, Grondin FR, Schenck-Gustafsson K, Yan AT. Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes. Am Heart J 2012;163(1):66-73.
18. Wizemann TM, Pardue M-L (eds). Exploring the Biological Contributions to Human Health: Does Sex Matter? Report of the Institute of Medicine. Washington, DC: National Academy Press, 2001.
19. Federman DD. The biology of human sex differences. N Engl J Med. 2006;354(14):1507-1514.
20. Mattison D, Zajicek A. Gaps in knowledge in treating pregnant women. Gend Med 2006;3(3):169-182.
21. Gray J. Why can't a woman be more like a man? Clin Pharmacol Ther 2007;82(1):15-17.
22. Abad-Santos F, Novalbos J, Gálvez-Múgica MA, Gallego-Sandín S, Almeida S, Vallée F, García AG. Assessment of sex differences in pharmacokinetics and pharmacodynamics of amlodipine in a bioequivalence study. Pharmacol Res 2005;51(5):445-452.
23. Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2009;48(3):143-157. (May 26, 2013)
24. Chen M-L, Lee S-C, Ng M-J, Schuirmann DJ, Lesko LJ, Williams RL. Pharmacokinetic analysis of bioequivalence trials: Implications for sex-related issues in clinical pharmacology and biopharmaceutics. Clin Pharmacol Ther 2000;68(5):510-521.
25. Meibohm B, Beierle I, Derendorf H. How important are gender differences in pharmacokinetics? Clin Pharmacokinet 2002;41(5):329-342.
26. Greenblatt DJ, von Moltke LL. Gender has a small but statistically significant effect on clearance of CYP3A substrate drugs. J Clin Pharmacol 2008;48(11):1350-1355.
27. Hu ZY, Zhao YS. Sex-dependent differences in cytochrome P450 3A activity as assessed by midazolam disposition in humans: a meta-analysis. Drug Metab Dispos 2010;38(5):817-812. (May 28, 2013)
28. Chetty M, Mattison D, Rostami-Hodjegan A. Sex differences in the clearance of CYP3A4 substrates: exploring possible reasons for the substrate dependency and lack of consensus. Curr Drug Metab 2012 Jul;13(6):778-786.
29. Aarnoudse AL, Dieleman JP, Stricker BH. Age- and gender-specific incidence of hospitalisation for digoxin intoxication. Drug Saf 2007;30(5):431-436.
30. Rathore SS, Wang Y, Krumholz HM. Sex-based differences in the effect of digoxin for the treatment of heart failure. New Engl J Med. 2002;347(18):1403-1411. (May 28, 2013)
31. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-533.
32. Yukawa M, Yukawa E, Suematsu F, Takiguchi T, Ikeda H, Aki H, Mimemoto M. Determination of digoxin clearance in Japanese elderly patients for optimization of drug therapy: a population pharmacokinetics analysis using nonlinear mixed-effects modelling. Drugs Aging 2011;28(10):831-841.
33. Ma RCW, Chan JCN. Type 1 diabetes. In: Schenck-Gustafsson K, DeCola PR, Pfaff DW, Pisetsky DS, eds. Handbook of Clinical Gender Medicine. Basel: Karger, 2012:268-272.
34. Chamnan P, Ma RCW, Chan JCN. Type 2 diabetes. In: Schenck-Gustafsson K, DeCola PR, Pfaff DW, Pisetsky DS, eds. Handbook of Clinical Gender Medicine. Basel: Karger, 2012:273-282.
35. Chamnan P, Simmons RK, Khaw KT, Wareham NJ, Griffin SJ. Estimating the potential population impact of stepwise screening strategies for identifying and treating individuals at high risk of Type 2 diabetes: a modelling study. Diabet Med 2012;29(7):893-904. (May 28. 2013)
36. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87(1):4-14. (May 28, 2013)
37. Kanaya AM, Grady D, Barrett-Connor E. Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med 2002;162(15):1737-1745. (May 28, 2013)